Background: The endothelium should be carefully evaluated when
choosing a surgical technique for cataract removal. Therefore, we aimed
to study the effects of different cataract surgery techniques on
endothelial cell loss in transplanted corneal grafts. Methods: A total
of 54 patients who received complicated cataract surgery in
post-penetrating keratoplasty (PKP) eyes at the Shandong Eye Institute
between February 2001 and June 2014 were included, and clinical records
were reviewed. Baseline demographic details, clinical characteristics,
endothelial cell density (ECD), and best-corrected visual acuity (BCVA)
were recorded. Wilcoxon rank-sum test and Wilcoxon signed-rank test were
used to test the equality of medians. A regression model was constructed
to compare the reduced rate of ECD. Results: Of the 54 eyes included in
this study, extracapsular cataract extraction (ECCE) was performed in 34
eyes of 33 patients (ECCE group) whereas phacoemulsification was
performed in 20 eyes of 20 patients (phacoemulsification group). There
was no significant difference in the median age (P = 0.081) or
preoperative ECD (P = 0.585) between the two groups. At 6 months after
cataract surgery, ECD in ECCE group was significantly higher than that
in phacoemulsification group (P = 0.043). In addition, the endothelial
cell loss rate in ECCE group was significantly lower than that in
phacoemulsification group at 2 months (P = 0.018), 4 months (P <
0.001), and 6 months (P < 0.001) after cataract surgery. Endothelial
cell loss rate after cataract surgery increased over the 6-month study
duration in both ECCE group (P < 0.001) and phacoemulsification group
(P < 0.001), but phacoemulsification resulted in a greater reduction
in ECD than that of ECCE in transplanted corneal grafts (P < 0.001).
There was no significant difference in postoperative BCVA between the
two groups (P = 0.065). Conclusion: ECCE is more suitable than
phacoemulsification in cataract surgery in complicated cataract after
PKP.

Introduction

Cataracts, a leading cause of blindness worldwide, are not only
largely senile or age-related in origin but also a well-recognized
complication of corneal transplantation. Underlying corneal disease
pathology, inadvertent injury to the lens during corneal
transplantation, and the use of therapeutic procedures such as
corticosteroidal agents after keratoplasty can induce cataracts.

In normal corneal physiology, loss of endothelial cells occurs
gradually during the aging process. However, with a corneal transplant,
the rate of endothelial cell loss accelerates significantly. After
penetrating keratoplasty (PKP), the annual rate of endothelial cell loss
averages 7.8% between the 3[sup]rd and 4[sup]th postoperative years and
4.2% between the 6[sup]th and 10[sup]th postoperative years.[sup][1],[2]
The reason underlying this phenomenon remains unclear. So far, this
effect may be explained, in part, by immunological mechanisms.

The degree of endothelial cell loss is unchanged between patients
after combined keratoplasty and cataract surgery versus staged
surgery.[sup][3] Ohguro et al .[sup][4] reported a similar rate of
endothelial cell loss in transplanted corneal grafts versus normal
corneas after extracapsular cataract extraction (ECCE) and posterior
chamber intraocular lens (PC-IOL) implantation. However, Kim et al
.[sup][5] found a higher rate of endothelial cell loss after cataract
extraction in transplanted corneal grafts than in normal corneas. In a
prospective randomized study, Acar et al. [sup][6] revealed that
transplanted corneal grafts after ECCE had a lower endothelial cell loss
rate than that of transplanted corneal grafts after phacoemulsification.
The endothelium should be carefully evaluated when choosing a surgical
technique for cataract removal in both normal and transplanted corneal
grafts. Therefore, it is necessary to study the effects of different
cataract surgery techniques on endothelial cell loss in transplanted
corneal grafts. This retrospective study compared the endothelial cell
density (ECD) and cell loss rate after ECCE versus phacoemulsification
in treating complicated cataract in post-PKP eyes.

Methods

Patients

This study was approved by the Institutional Review Board of the
Shandong Eye Institute. We retrospectively reviewed medical records.
Patients who received phacoemulsification or ECCE in eyes with
complicated cataract and previous PKP were included. Cases with the
following conditions were excluded: Uveitis, proliferative diabetic
retinopathy, preoperative ocular hypertension or newly detected
glaucoma, low baseline endothelial cell count (<1000 cells/mm
[sup]2), prior intraocular surgery except PKP, preoperative factors
known to prolong surgical time (i.e., peripheral anterior synechiae,
shallow anterior chamber, and pseudoexfoliation), combined cases of
cataract extraction and other ocular surgery, episodes of immunologic
graft reaction after PKP, or complications up to 6 months after cataract
surgery. A total of 54 cases were included in this study. These cases of
cataract surgeries were carried out between February 2001 and June 2014
at Shandong Eye Institute, China.

The surgical techniques are described here in brief. Periocular
anesthesia and preoperative digital ocular massage were administered to
most eyes. In most eyes, ECCE was performed using the W-shaped incision
[Figure 1],[sup][8] followed by a continuous curvilinear capsulorhexis
(CCC). A PC-IOL was placed. The wound was sutured using a 10-0 nylon
suture. In most eyes, phacoemulsification was performed via a 3.0 mm
clear corneal incision and a CCC whose diameter is approximately 5.5 mm.
A PC-IOL was placed. No sutures were used for closure. All the surgeries
were performed by two very sophisticated surgeons. Central corneal ECD,
percentage of hexagonal endothelium, and BCVA at 2, 4, and 6 months
after cataract surgery were recorded.{Figure 1}

Statistical analysis

Measurement data were processed using SAS 6.12 (SAS Institute Inc.,
Cary, NC, USA). Nonparameter statistical methods such as Wilcoxon
rank-sum test and Wilcoxon signed-rank test were used to test the
equality of medians. Endothelial cell loss rate was expressed as a
percentage of the preoperative cell density. A regression model was
constructed to compare the cell loss rate of ECD with time between the
two groups. A P < 0.05 was considered significantly different.

Since the age in ECCE group was not normally distributed
(Shapiro-Wilk test, P = 0.008), Wilcoxon rank-sum test was used to test
the equality of the median age between the two groups. The median age of
ECCE and phacoemulsification groups was 60.0 years and 51.5 years,
respectively, and there was no statistically significant difference ( W
= 452.5, P = 0.081, two-tailed). Since the preoperative ECD in
phacoemulsification group was not normally distributed (Shapiro-Wilk
test, P = 0.004), Wilcoxon rank-sum test was used to test the equality
of the median ECD between the two groups. The median ECD of ECCE and
phacoemulsification groups was 1968 cells/mm [sup]2 and 1882 cells/mm
[sup]2, respectively, and there was no statistically significant
difference ( W = 519, P = 0.585, two-tailed) [Table 1].

Since the ECD in phacoemulsification group at 2, 4, and 6 months
after cataract surgery was not normally distributed (Shapiro-Wilk test,
P = 0.004, 0.003, and 0.003, respectively), Wilcoxon rank-sum test was
used to test the equality of median between the two groups. The median
ECD had no statistically significant difference between the two groups
at 2 ( W = 514, P = 0.525) and 4 months postoperatively ( W = 466, P =
0.136); however, at 6 months after cataract surgery, ECCE group had a
significantly higher median ECD than phacoemulsification group ( W =
437, P = 0.043, two-tailed) [Table 3]. Wilcoxon rank-sum test was also
used to compare the median cell loss rate between the two groups.
Statistically significant difference in the median cell loss rate was
noted at 2 ( W = 418, P = 0.018), 4 ( W = 251, P < 0.001), and 6
months ( W = 211, P < 0.001) between the two groups after PKP [Table
3].

where [micro] and [sz] denote the common intercept and slope,
a[sub]i and [sz][sub]i denote the intercept and slope corresponds to
ECCE group when i = 1 and phacoemulsification group when i = 2,
respectively, ? denotes the error term. The estimated result is [sz]
[sz][sub]1– [sz] [sz][sub]2= −0.001 ( P < 0.001),
meaning that slope of phacoemulsification group was significantly
steeper than that of ECCE group. In other words, ECD reduced faster when
phacoemulsification was used rather than ECCE in transplanted corneal
grafts.

Since BCVA after cataract surgery in both groups was not normally
distributed (Shapiro-Wilk test, P < 0.001 in ECCE group and P = 0.016
in phacoemulsification group), Wilcoxon rank-sum test was used to test
the equality of the median BCVA between the two groups. The median BCVA
in ECCE and Phacoemulsification groups was 0.200 and 0.300,
respectively, and Wilcoxon rank-sum test indicated no statistically
significant difference ( W = 832.5, P = 0.065, two-tailed).

Discussion

In transplanted corneal grafts, endothelial cell loss after
cataract surgery can result from multiple factors: Mechanical damage to
the grafted endothelium during cataract surgery or IOL implantation,
ocular hypertension, and postoperative immunological reactions. We
retrospectively reviewed 54 cases of patients who received complicated
cataract surgery after PKP and added new discoveries to complicated
cataract surgery in post-PKP eyes. Based on our study,
phacoemulsification damaged more endothelial cells than ECCE at 6 months
after cataract surgery in transplanted corneal grafts, and
phacoemulsification resulted in a significantly higher endothelial cell
loss rate than ECCE in transplanted corneal grafts at 2, 4, and 6 months
after surgery.

In normal corneas, there is no significant difference between the
effects of ECCE and phacoemulsification on the endothelial cell loss
rate.[sup][9] Bourne et al. [sup][10] found a similar 10% decrease in
endothelial cell count after phacoemulsification and conventional ECCE;
the authors suggested that ECCE was preferred over phacoemulsification
for hard nuclear cataracts removal, given that phacoemulsification
caused greater endothelial cell loss rate than ECCE in such cases.
Similarly, Acar et al. [sup][6] showed that ECCE caused less endothelial
cell damage than phacoemulsification in post-PKP eyes with hard nuclear
cataracts in a clinical trial of 26 patients during the 6-month
follow-up, and they also observed that phacoemulsification resulted in a
significantly greater endothelial cell loss rate in post-PKP eyes (16
eyes) than eyes with no previous surgery (20 eyes).[sup][11] We found
that the ECD was significantly reduced in the phacoemulsification group
versus the ECCE group at 6 months after cataract surgery in transplanted
corneal grafts. In addition, phacoemulsification resulted in a
significantly higher endothelial cell loss rate than ECCE in
transplanted corneal grafts at 2, 4, and 6 months after surgery. Thus,
our study provides a clear comparison of the effects of ECCE and
phacoemulsification on the endothelial cell loss rate in post-PKP eyes
with complicated cataract for the first time.

It was found that ECD was not significantly different before and
after IOL implantation in transplanted corneal grafts during the 6-month
follow-up in 26 eyes.[sup][12] Ohguro et al .[sup][4] reported no
significant difference in the endothelial cell loss rate 3 months after
ECCE with PC-IOL implantation in transplanted corneal grafts (6.2%, n =
18) and normal corneas (4.7%, n = 18) in a case series. The endothelial
cell loss rate increased gradually over 6 months after cataract surgery
and IOL implantation in transplanted corneal grafts in our series ( n =
54).

In cases of uneventful ECCE, the mean endothelial cell loss rate
varies from 6% to 17% whereas the mean endothelial cell loss rate in
complicated cases exceeds 40%.[sup][13] We found that the median
endothelial cell loss rate was 7.3% at 2 months after ECCE and 7.3% at 2
months after phacoemulsification in post-PKP eyes; the median
endothelial cell loss rate was 10.2% at 4 months after ECCE and 17.0% at
4 months after phacoemulsification in post-PKP eyes; finally, the median
endothelial cell loss rate was 12.1% and 23.0% at 6 months after ECCE
and phacoemulsification, respectively, in post-PKP eyes. Moreover, the
median endothelial cell loss rate was significantly higher in the
phacoemulsification group than in the ECCE group at 2, 4, and 6 months
after cataract surgery in transplanted corneal grafts.

In our study, the ECD of transplanted corneal grafts in the
phacoemulsification group was noticed to reduce faster than that in the
ECCE group. The major reasons for this natural phenomenon are as
follows. First, the maneuverability of ECCE is high, and thus in ECCE
group, the incision can be created in a large size (W-shape) and the
nucleus can be removed conveniently. It was reported that W-shaped
incision benefited the extraction of hard nucleus, the implantation of
IOL with large optic zone, and reduced the time to reach refractive
stability.[sup][8] Second, the nucleus of complicated cataract after PKP
is usually hard (the percentage of nuclear hardness ≥IV was
83% in our cases), and thus in these cases, more energy is required in
phacoemulsification, which deteriorates the endothelial cells.
Concerning ECCE, ample training, and a large size incision can make the
extraction of hard nucleus be more convenient, and meanwhile, the number
and quality of corneal endothelial cells can be maintained well. In
contrast, the stability of anterior chamber is hard to be maintained in
phacoemulsification surgery. Despite the premise of ample training, it
is seldom accomplished to decrease the energy used in
phacoemulsification when dealing with hard nucleus. Therefore, corneal
endothelial cells may be damaged more severely in phacoemulsification
than ECCE.

Accumulating evidence supports that some putative progenitors for
the corneal endothelium reside in the transition area between the
peripheral corneal endothelium and the anterior nonfiltering portion of
the trabecular meshwork,[sup][14] and microenvironment plays an
important role in determining the proliferative capacity of human
corneal endothelial cells.[sup][15] The discovery that
phacoemulsification resulted in a significantly higher postoperative
endothelial cell loss rate than ECCE in transplanted corneal grafts may
be partly explained by a conjecture that phacoemulsification damages
more putative progenitors for corneal endothelium and affects
microenvironment of human corneal endothelial cells more than ECCE does;
however, the lack of evidence does not permit anyone to unravel it at
present. The possible discrepancy of postoperative viscoelastics residue
levels between the two groups may be another factor responsible for the
discovery.

There was significant progress in phacoemulsification in the past
years, and corneal endothelial cells can be effectively preserved.
Microincision cataract surgery technique effectively preserves corneal
endothelial cells and reduces risk of corneal edema.[sup][16] Micropulse
technique increases anterior chamber stability [sup][17] and decreases
thermal effect.[sup][18] Torsional ultrasound mode reduces
phacoemulsification time and energy.[sup][19] New ophthalmic
viscosurgical devices, such as Viscoat, Provisc, and soft-shell
technique, decrease thermal effect.[sup][20] Thus, in certain cases of
complicated cataract after PKP such as cases in which nuclear hardness
is ≤III, better postoperative visual acuity is demanded, and
an advanced technology IOL is preferred, phacoemulsification should be
suggested. Our study has potential limitations as a retrospective cohort
study which spanned 13 years. The 6-month study duration was relatively
short. Further randomized controlled trials are needed with a larger
sample size and longer study duration to further elucidate this topic.

In conclusion, ECCE causes less damage than phacoemulsification on
the vulnerable endothelium in transplanted corneal grafts up to 6 months
after cataract surgery. Based on our results, ECCE causes less damage
than phacoemulsification on the vulnerable endothelium.